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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-10-3265. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3265v1 101/11/4520    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by McFarland, H. I. Articles by Rosenberg, A. S. Search for Related Content PubMed PubMed Citation Articles by McFarland, H. I. Articles by Rosenberg, A. S. Related Collections Immunobiology Transplantation Gene Expression Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2003, Vol. 101, No. 11, pp. 4520-4528 IMMUNOBIOLOGY Signaling through MHC in transgenic mice generates a population of memory phenotype cytolytic cells that lack TCR Hugh I. McFarland, Susan A. Hansal, Diane I. Morris, Daniel W. McVicar, Paul E. Love, and Amy S. Rosenberg From the Division of Therapeutic Proteins, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD; Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Frederick, MD; and Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. We constructed a chimeric molecule, composed of the T-cell receptor (TCR)– chain fused to the extracellular domains of a prototypical allogeneic major histocompatibility complex (MHC) class I molecule, Dd, to assess whether such a construct could affect Dd allospecific responses in vitro and in vivo. To generate cytotoxic T lymphocytes (CTLs) expressing the construct, Dd- was targeted to lymphocyte populations in transgenic mice by placing its expression under control of the CD2 promoter. In response to ligation of Dd, lymphocytes from transgenic mice expressing high levels of Dd- are activated to proliferate and kill cells binding to Dd, despite the near total loss of CD8+ T cells in these mice. Thus, the Dd- cytolytic cell was found not to be a conventional CD8+ CTL, but rather an unusual T lineage cell (CD3-CD5+Thy1.1+) that lacked or TCRs, as well as CD4 and CD8 coreceptors, but expressed surface markers strikingly similar to memory CTLs, including CD44, Ly-6C, and CD122. These cells originate in the thymus and potently veto responses to Dd in vitro. Lacking TCRs, these veto cells are unlikely to mediate graft-versus-host disease (GVHD) and thus may be useful as a cellular therapy for therapeutic deletion of alloreactive T cells in the settings of graft rejection and GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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